Adrenomedullin worsens skin necrosis in rats subjected to vincristine-induced extravasation.

BACKGROUND: Extravasation of vesicant drugs such as vinca alkaloids causes severe injury, which may range from erythema to skin necrosis or ulceration. The skin necrosis may not be fully evident until several weeks or months after the initial damage, and may require surgical intervention. The main treatments for vincristine extravasation are hyaluronidase injection and topical warming, and the aim of treatment is to increase the clearance of the drug from the extravasation site. AIM: To investigate the effect of adrenomedullin, a potent vasodilatory peptide, in rats subjected to vincristine-induced extravasation. METHODS: In total, 36 Wistar albino rats were given intradermal injection of vincristine and saline. The rats were assigned to one of three treatment groups (adrenomedullin, adrenomedullin + hyaluronidase, or hyaluronidase), a control group given vincristine only, or a sham group (saline). Tissue superoxide dismutase (SOD), glutathione peroxidase, malondialdehyde (MDA) and protein content were evaluated in skin biopsies taken on day 22. The ulcer size and histopathological grading scores were also recorded. RESULTS: SOD levels were significantly increased by adrenomedullin and increased by hyaluronidase. Glutathione peroxidase levels were significantly decreased in all four vincristine groups. Tissue MDA levels were highest in the adrenomedullin group. In all four vincristine groups, MDA levels were reduced, indicating preservation from tissue injury. Protein carbonyl (PCO) content levels in the adrenomedullin group were significantly greater than in the other three study groups (P < 0.05). In contrast, PCO levels in the hyaluronidase group were significantly lower than in the other three groups. CONCLUSIONS: In this animal model of vincristine-induced extravasation, antioxidant status and histology were preserved by hyaluronidase but worsened by adrenomedullin.

Effect of proanthocyanidin, arginine and glutamine supplementation on methotrexate-induced gastrointestinal toxicity in rats.

Methotrexate is a folate antagonist that is commonly used as an antitumor and antiarthritic drug. The aim of this study was to investigate the possible roles of exogenous glutamine (Glu), arginine (Arg) and proanthocyanidin (PA) on gut protection from methotrexate-induced intestinal damage in rats. Experimental rats were separated into eight groups. The first (sham) group received a 0.9% NaCl solution alone. The second group received intraperitoneal injections of methotrexate (20 mg/kg/day) administered on day 4 of the experiment and continued for 5 days. Rats in the other six groups were administered PA, Glu, Arg, Glu+PA, Arg+PA or Glu+Arg orally by gavage together with methotrexate and animals were sacrificed on day 8 of the experiment. All animals were sacrificed 4 days after methotrexate injection for histopathological analysis, tissue glutathione peroxidase, malondialdehyde and superoxide dismutase assays. Proanthocyanidin and Glu decreased the severity of intestinal injury and oxidant injury as evident by histopathology and changes in malondialdehyde levels. Histological analysis confirmed that PA and to a lesser extent Glu supplementation were more favorable than Arg for the protection of the small intestine from methotrexate-induced injury.

Evaluation of pertussis immunity status in schoolchildren immunized with whole-cell vaccine.

It has recently been reported that the worldwide increase in the number of pertussis cases is a result of the waning of whole-cell vaccine-induced immunity. Thus, in this study, we aimed to investigate the pertussis immunity status of primary and secondary school students in a district of Ankara, Turkey. A total of 997 healthy students, aged 9-17 years, who had been immunized with four doses of whole-cell pertussis vaccine were included in the study. The subjects were divided into two age groups: 9-14 and 15-17 years. To determine the immune status, serum levels of IgG anti-pertussis toxin (aPT) antibody were tested by in-house ELISA and arbitrarily evaluated as non-immune [< 10 ELISA units (EU)/ml], immune (10-100 EU/ml), and recent infection (> 100 EU/ml). Serum samples of 997 students (559 females, 438 males) aged between 9 and 17 years (mean 13.02 +/- 2.25, median 13 years) were tested. Non-immune, immune and recent infection levels of aPT were found in 27.3%, 59.3% and 13.4% of individuals, respectively. The immune group did not have statistically significant differences between males and females (P = 0.68). In the 9-14 and 15-17 years age groups, serum aPT antibody levels 10 EU/ml were 73.1% and 72.2%, respectively, which did not represent any statistical difference (P = 0.81). Students aged 15-17 years had a higher immunity rate than the 9-14 years group, and the percentage of students with recent infection in the 9-14 years group was higher than the 15-17 years group (P < 0.001). The peak age of non-immunized subjects was 9 years (47.0%), and decreased to a minimum at age 12-13 years, and began to increase again from age 13-14 years. In contrast, the ratio of recent infection was least at age 9-10 years, began to increase, and reached a peak at 12 years, and then decreased. On the other hand, it was observed that household size and monthly income were not associated with the immunity status (P = 0.65, P = 0.37, respectively). The results of the present study show that levels of antibody against pertussis decreased in the younger age groups and, as a result, there is an increase in the number of pertussis cases. Thus, in order to decrease the incidence of pertussis and protect infants, we recommend the application of booster doses at regular intervals.

Varicella vaccination in children with lymphoma and solid tumours.

BACKGROUND: Varicella infection can be a severe disease, especially in immunosuppressed patients. Here, experience with live varicella vaccine to prevent varicella infection is reported in children who were undergoing treatment for lymphoma and solid tumours. METHODS: 40 children, aged between 12 months and 15 years with no clinical history of varicella, were vaccinated with live varicella vaccine. All received two doses of the vaccine subcutaneously 4 weeks apart. Serum samples were taken before the first dose and 6 weeks after the second dose of vaccine. RESULTS: Before vaccination, 32 patients were seronegative for varicella and eight were seropositive. Seroconversion was observed 6 weeks after the second dose in 24 of the 32 (75%) seronegative children. In 4 of 8 previously seropositive patients, antibody titres increased after immunisation. Zoster infection occurred 5 weeks after the second dose of vaccine in only one previously seronegative child. 7 children, who had responded to the vaccine, have been exposed to varicella in their families or in school without contracting clinical disease. CONCLUSION: Although the small number of patients in our group prevents us from drawing definitive conclusions, the varicella vaccine seems to be well tolerated and can be administered to children with lymphoma and solid tumours undergoing treatment.

Malignant fibrous histiocytoma in a child. A case report and review of the literature.

Malignant fibrous histiocytoma (MFH) is the most common soft tissue sarcoma of late adult file. It is extremely rare in children, though, and its existence in the pediatric population remains controversial. Although the most common site of tumor in children is the extremities, which is similar to findings of adults' series, different sites have been reported in children. Because of the rarity of this tumor in childhood, the approach to treatment of MFH is based primarily on the experience with adults. We present the clinical and pathologic features of an eight-year-old boy with MFH located on his left retroperitoneum and also review the literature.

Effect of iron therapy on the whole blood platelet aggregation in infants with iron deficiency anemia.

This study was performed to investigate the platelet aggregation alterations in whole blood samples of infants with iron deficiency anemia. Platelet aggregation induced by various concentrations of adenosine diphosphate (ADP) and collagen was studied with impedance aggregometry in 25 patients before and after oral iron therapy and in 12 children of the control group. The posttreatment mean maximum aggregation values were significantly higher (p<0.01) and the posttreatment mean aggregation times were significantly lower (p<0.01) in the study group at all concentrations of ADP and collagen. The aggregation time and maximum aggregation values revealed no significant difference except for the maximum aggregation value at 5 microM ADP (p<0.05) between the study group after therapy and the control group. The differences between the pretreatment and posttreatment mean platelet counts and mean platelet volume values in the study group were statistically significant (p<0.01), whereas those values in the study group after therapy and in the control group were not significantly different. We conclude that iron deficiency anemia in infants, even without clinically meaningful platelet abnormality, may cause dysfunction of the ex vivo whole blood platelet aggregation, and can be reversed by iron therapy. Further studies should be carried out at the enzymatic level to determine whether this platelet aggregation dysfunction in iron deficiency anemia is due to a deficiency in the activation of iron-containing enzymes.

Primary ovarian lymphoma in an infant: report of a case.

Primary ovarian malignant lymphomas are rarely encountered in children. We present herein the unusual case of an 11-month-old female infant with primary bilateral non-Hodgkin's lymphoma of the ovaries who was treated by bilateral salpingo-oophorectomy followed by chemotherapy. The clinicopathological features of this rare entity are discussed, focusing special emphasis on the diagnostic and therapeutic strategies.

Neuroblastoma with spermatic cord metastasis in a child: sonographic findings.

We report a case of neuroblastoma in a patient who had no involvement of the spermatic cord at diagnosis but who developed spermatic cord metastasis 2 months later. The metastasis appeared on sonography as a hypoechoic, highly vascular, fusiform, hard, 14x10x7 mm mass located in the right inguinal canal and extending into the scrotum. The diagnosis of spermatic cord metastasis was confirmed by resection and histopathologic examination. We recommend that the scrotum and spermatic cord be evaluated by high-resolution sonography in children with neuroblastoma, both at the time of diagnosis and during follow-up.

Malignant hypertension and paraganglioma in a 14-year-old girl.

A 14-year-old girl presented with malignant hypertension. Physical examination and abdominal computerized tomography revealed a paraaortic mass. Urinary catecholamines, serum renin, and aldesterone levels were high. The mass was totally excised and a paraganglioma of the organ of Zuckerkandl was confirmed. The hypertension resolved after surgery.

Acquired pseudocholinesterase deficiency after high-dose cyclophosphamide.

Succinylcholine, a depolarizing neuromuscular blocking agent used in anesthesia is hydrolyzed in the plasma by the enzyme pseudocholinesterase (PSC). Conditions associated with reduced PSC activity lead to sustained action of succinylcholine and result in prolonged apnea. Cyclophosphamide is an inhibitor of PSC and its suppressive effect may be dose-dependent. We report a case of severe PSC deficiency after high-dose cyclophosphamide at 7 g/m2. The patient received succinylcholine during anesthesia 9 h after chemotherapy and developed prolonged apnea. This case highlights the potential risk of drug-induced PSC deficiency and cautions the use of depolarizing muscular relaxants soon after high-dose cyclophosphamide.

Primary intracranial germ cell tumors in children: a report of eight cases and review of the literature.

This study was conducted to evaluate the signs and symptoms on admission, diagnosis, localization, therapy, and survival of patients with primary intracranial germ cell tumors (PICGCT). Eight patients with surgically confirmed PICGCTs were treated and followed up at Hacettepe University's Department of Pediatric Oncology between 1974 and 1995. While one patient was admitted with a second recurrence of her disease, the others were admitted or referred primarily to our institution. In this period, 357 germ cell tumor and 684 primary intracranial malignant tumors were diagnosed and treated at our institution. Thus, PICGCTs comprised 1.1 percent of the primary intracranial malignant tumors and 2.2 percent of the germ cell tumors. There were four females and four males and the median age was eight years (13 months to 12 years). On admission, the most common symptoms were diabetes insipidus (3/8) and vomiting (3/8). One patient also and Down's syndrome. Locations of the tumors were suprasellar in three, in the third ventricle in two, and in the cerebral parenchyma, and pineal and hypothalamic regions in the remainder. There were germinomas, three malignant teratomas, and two mixed germ cell tumors. Only two patients could be treated with appropriate and adequate chemotherapy and radiotherapy. Three patients died: one in the postsurgical period, one after the third surgical approach and one 11 months after the diagnosis of progressive disease; three were lost to follow-up. The remaining two patients (with second recurrence and disseminated disease) are alive and without disease. Our experience with these patients demonstrated that appropriate and adequate chemotherapy is as effective a treatment as radiotherapy, even with recurrence of the disease.

Comparison of the efficacy and side-effects of ondansetron and metoclopramide-diphenhydramine administered to control nausea and vomiting in children treated with antineoplastic chemotherapy: a prospective randomized study.

UNLABELLED: Nausea and vomiting following antineoplastic therapy in patients receiving chemotherapy remains a problem. To prevent nausea and vomiting due to antineoplastic therapy, many types of drugs have been used. Ondansetron and the combination metoclopramide-diphenhydramine have been widely used in children. In this prospective randomized study these drugs were compared both for their efficacy and side-effects in children treated with antineoplastic chemotherapy (with and without cisplatin) the number of chemotherapy courses being equal in both groups. Ondansetron gave complete anti-emetic cover in five of nine courses in patients treated with cisplatin. Metoclopramide-diphenhydramine gave complete anti-emetic cover in one out of nine courses, and 17 out of 23 courses in patients treated without cisplatin. Metoclopramide-diphenhydramine produced side effects in nine courses whereas ondansetron produced side-effects in three courses. CONCLUSION: Ondansetron appeared to be superior to metoclopramide-diphenhydramine in the control of emesis induced by chemotherapy regimens containing cisplatin. The results of the present prospective randomized study indicate that ondansetron is a useful anti-emetic in the treatment of chemotherapy-induced emesis.

Germ cell tumours in a brother and sister.

In familial germ cell tumour cases, a normal chromosomal karyotype pattern is rare. We report the findings of germ cell tumours in two siblings with a normal chromosomal karyotype. One of these patients had dysgerminoma in the right ovary and was treated successfully for this. At present, she is 23 years old and has two daughters. The other patient is a 15-year-old boy, who is the brother of the first patient and has mediastinal embryonal carcinoma. Although ultrasonography of the testes showed irregularity in the shape and non-homogeneity of the parenchyma, histopathological examination was found to be normal at the time of diagnosis. At present, he is doing well and his chemotherapy is continuing. Both of them have a normal chromosomal karyotype, 46, XX and 46, XY, respectively. We suggest that children who have a sibling with germ cell tumour should be carefully assessed for development of another germ cell tumour.

The frequency of resistance to erythromycin in group A streptococci in Ankara.

UNLABELLED: The frequency of resistance to erythromycin of group A beta-haemolytic streptococci in the last 7 years was determined in three medical centres in Ankara. While all group A beta-haemolytic streptococci strains were susceptible to penicillin, a gradual increase in resistance to erythromycin until 1992 was observed. However, a substantial increase in erythromycin resistance occurred in 1993 when newer macrolides became available and were widely used in the latter part of 1992. CONCLUSION: The data show that frequent testing for resistance to erythromycin of group A beta-haemolytic streptococci is required for the use of this antibiotic in our country.

The platelet aggregation in children with epilepsy receiving valproic acid.

This study was performed to evaluate the aggregation changes in the whole blood samples of children with epilepsy receiving valproic acid. A total of 25 patients and 15 healthy volunteer adults were included in the study. Platelet aggregation study was performed in whole blood by impedance aggregometry. Platelet counts, the bleeding times, and clotting times of the patients were within normal limits. The aggregation time and maximum aggregation values revealed no significant difference except for those with 2 mu g/ml collagen (p < 0.01) between the two groups. Serum valproic acid levels of the children did not correlate with the maximum aggregation values induced by different concentrations of aggregating agents except for 20 mu M ADP (r = -0.430, p < 0.05). We concluded that the use of valproic acid does not result in thrombocytopenia and platelet dysfunction within therapeutic limits and the drug is reliable in the management of epilepsy.

The normalization period of platelet aggregation in newborns.

This study was performed to investigate the normalization period of the transient platelet dysfunction of newborns. A total of 43 healthy newborns of healthy mothers who had received no medication for at least 14 days prior to delivery were included in the study. Venous blood samples of 44 healthy volunteer adults were used as control. Platelet aggregation study was performed in whole blood by impedance aggregometry. Collagen or ADP was used as the aggregating agent. In the platelet aggregation studies using collagen, maximum aggregation values in the first three days of life were lower than those of adults (p < 0.001). These lower values were improved and reached adult values between the 5th and 9th day of life. Lower maximum aggregation values were observed in newborns in comparison with those of adults when ADP was used, but the difference was not significant except for 5 microM concentration of ADP. There was no significant difference between the aggregation time of the collagen and ADP groups (p > 0.05). In conclusion, the platelet responses to ADP and collagen were increased in newborns as the age progressed and reached normal levels between 5th and 9th day of life. If platelet dysfunction does exist after the 10th day of life, this finding may be due to either simple prolongation of the physiological phenomenon or platelet disorders.